Pyrazolo [1,5-C] quinazoline derivatives and their use in treating allergic conditions

ABSTRACT

Compounds are provided having the structure ##STR1## wherein R 1  is carboxyl; hydroxymethyl; CO 2  R 3  wherein R 3  is lower alkyl, Li + , Na +   or K +  ; or ##STR2## R 2  is hydrogen, lower alkyl, aryl or trifluoromethyl; and X is hydrogen, lower alkyl, lower alkoxy, halogen (Cl, Br and F), or trifluoromethyl. These compounds are useful as anti-allergics.

DESCRIPTION OF THE INVENTION

The present invention relates to pyrazolo[1,5-c]quinazoline derivativesof the structure ##STR3## wherein R¹ is carboxyl; hydroxymethyl; CO₂ R³wherein R³ is lower alkyl, Li⁺, Na⁺ or K⁺ ; or ##STR4## R² is hydrogen,lower alkyl, aryl, or trifluoromethyl; and X is hydrogen, lower alkyl,lower alkoxy, halogen (Cl, Br or F) or trifluoromethyl.

Preferred are those compounds of Formula I wherein R¹ is carboxyl,hydroxymethyl, or lower alkoxycarbonyl, R² is hydrogen, and X ishydrogen.

Unless otherwise indicated the term "lower alkyl" or "alkyl" as employedherein includes both straight and branched chain radicals of up to eightcarbon atoms, preferably up to and including 5 carbon atoms, forinstance, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl,isobutyl, n-pentyl, n-hexyl, isohexyl, n-heptyl, 4,4-dimethylpentyl,n-octyl, 2,2,4-trimethylpentyl, and the like.

Unless otherwise indicated, the term "lower alkoxy" or "alkoxy" includesstraight and branched chain radicals which correspond to the above loweralkyl groups attached to an oxygen atom.

Unless otherwise indicated, the term "aryl" as employed hereincontemplates monocyclic carbocyclic aryl radicals, for instance, phenyland substituted phenyl radicals, such as lower alkyl phenyl (e.g., o-,m- or p-tolyl, ethylphenyl, butylphenyl, and the like), di(loweralkyl)phenyl (e.g., 2,4-dimethylphenyl, 3,5-diethylphenyl, and thelike), halophenyl (e.g., chlorophenyl, bromophenyl, iodophenyl,fluorophenyl).

The compounds of Formula I of the invention may be prepared by severalmethods.

One method involves preparation of compounds of the structure ##STR5##wherein R⁴ is hydrogen or lower alkyl, and X and R² are as definedhereinbefore. The Formula II compounds are prepared by reactingcompounds of the structure ##STR6## with an acylating agent which may bean aliphatic carboxylic acid of the structure

    R.sup.2 COOH                                               (IV)

or aliphatic carboxylic acid halide of the structure

    R.sup.2 COHal                                              (V)

wherein Hal is Cl or Br,

or an aliphatic acid anhydride of the structure

    (R.sup.2 CO).sub.2 O                                       (VI)

or mixtures of any or all of the above (IV, V and/or VI), at atemperature within the range of from about -30° C. to about 350° C.,preferably from about 0° C. to about 250° C., for periods of 0.5 to 48hours.

The Formula III compounds may be prepared as described in U.S. Pat. No.3,899,508.

Compounds of Formula I wherein R¹ is ##STR7## may be prepared byreacting a 5-(optionally substituted2-aminophenyl)-1H-pyrazole-3-methanol, that is ##STR8## or a saltthereof, with an aryl or aliphatic carboxylic acid of the structure

    R.sup.2 COOH                                               (VIII)

at a temperature within the range of from about 0° to about 320° C., andpreferably from about 25° to 260° C. for periods of 0.5 to 48 hours.

The Formula VII compound may be prepared by reducing an alkyl ester of5-(optionally substituted 2-aminophenyl)-1H-pyrazole-3-carboxylic acid(prepared as described in U.S. Pat. No. 3,899,508) with a reducing agentsuch as lithium borohydride (LiBH₄) in an inert solvent such astetrahydrofuran.

Compounds of Formula I wherein R¹ is hydroxymethyl may be prepared byacid or base hydrolysis of compounds of Formula I wherein R¹ is ##STR9##

Compounds of Formula I in the form of Li⁺, Na⁺ or K⁺ salts, that is R¹is COO.sup.⊖ Li.sup.⊕, COO.sup.⊖ Na.sup.⊕ or COO.sup.⊖ K.sup.⊕ may beprepared by neutralizing a pyrazolo[1,5-c]quinazoline-2-carboxylic acidof the invention, that is ##STR10## with an appropriate lithium, sodiumor potassium salt, such as sodium or potassium carbonate or sodium orpotassium hydroxide.

The compounds of Formula I, and their pharmaceutically acceptable salts,are useful in treating various allergic conditions in mammalian speciessuch as mice, cats, dogs, etc., when administered in amounts rangingfrom about 1 milligram to about 500 milligrams per kilogram of bodyweight per day. The compounds can be used prophylactically ortherapeutically to treat various allergic and immunological disordersand in particular to treat certain types of asthma, hay-fever, andrhinitis. A preferred dosage regimen would be from about 3 milligrams toabout 200 milligrams per kilogram of body weight per day administered ina single dose or plurality of divided doses.

The compounds of Formula I, and the pharmaceutically acceptable saltsthereof, are orally active as anti-allergics and inhibit the effects ofcertain antigen-antibody reactions and in particular inhibit the releaseof mediators such as histamine. The anti-allergy activity of thesecompounds is determined by the reaginic antibody induced passivecutaneous anaphylaxis (PCA) reaction in rats and inhibition of histaminerelease from mast cells. See Bach, Immediate Hypersensitivity:Laboratory Models and Experimental Findings, Ann. Rep. Med. Chem.,7:238-248 (1972), for a discussion of the predictability of clinicalefficacy of compounds active in the PCA. In addition anti-allergyactivity of these compounds is determined by inhibition of histaminerelease from mast cells according to a modified procedure based on theprocedure described by L. G. Garland et al, British Journal ofPharmacology, Vol. 50, p. 137 (1974).

A compound of Formula I, or a salt thereof, can be administered by theinhalation of an aerosol or powder as described in U.S. Pat. No.3,772,336 (i.e., breathing finely divided particles of the activeingredient into the lungs), orally, or parenterally. Powders can beprepared by comminuting the active ingredient with a similarlycomminuted diluent such as starch or lactose. Suitable forms for oraladministration include capsules, tablets, and syrups, and a suitableform for parenteral administration is a sterile injectable. Such unitdosage forms are prepared by compounding with a conventional vehicle,excipients, binders, preservatives, stabilizers, flavoring agents or thelike as called for by acceptable pharmaceutical practice. Also, thecompounds of this invention can be formulated with otherpharmaceutically active compounds such as bronchodilators, steroids,antihistamines, etc.

The compounds of the present invention in the described dosages may beadministered orally; however, other routes such as intraperitoneally,subcutaneously, intramuscularly or intravenously may be employed.

The active compounds of the present invention are orally administered,for example, with an inert diluent or with an assimilable ediblecarrier, or they may be enclosed in hard or soft gelatin capsules, orthey may be compressed into tablets, or they may be incorporateddirectly with the food of the diet. For oral therapeutic administration,the active compounds of this invention may be incorporated withexcipients and used in the form of tablets, troches, capsules, elixirs,suspensions, syrups, wafers, chewing gum, and the like. The amount ofactive compound in such therapeutically useful compositions orpreparations is such that a suitable dosage will be obtained.

The tablets, troches, pills, capsules and the like may also contain thefollowing: a binder such as gum tragacanth, acacia, corn starch orgelatin; an excipient such as dicalcium phosphate, a disintegratingagent such as corn starch, potato starch, alginic acid and the like; alubricant such as magnesium stearate; and a sweetening agent such assucrose, lactose or saccharin may be added or a flavoring agent such aspeppermint, oil of wintergreen, or cherry flavoring. When the dosageunit form is a capsule, it may contain in addition to materials of theabove type a liquid carrier such as a fatty oil. Various other materialsmay be present as coatings or to otherwise modify the physical form ofthe dosage unit, for instance, tablets, pills or capsules may be coatedwith shellac, sugar, or both. A syrup or elixir may contain the activecompounds, sucrose as a sweetening agent, methyl and propyl parabens aspreservatives, a dye and a flavoring such as cherry or orange flavor. Ofcourse, any material used in preparing any dosage unit form should bepharmaceutically pure and substantially non-toxic in the amountsemployed.

The following Examples further illustrate and represent preferredembodiments of the invention. All temperatures are expressed in degreesCentigrade.

The letter "(d)" following a melting point indicates at least someapparent decomposition was observed. The term "stripped" also meansevaporation.

EXAMPLE 1 Pyrazolo[1,5-c]quinazoline-2-carboxylic acid

3.0 g (0.0148 mole) of 5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acidis suspended in 21 ml of 97+% HCOOH, and the reaction mixture heated inan oil bath at 100° for 2 hours. The reaction mixture is cooled, dilutedwith water (75 ml), stirred for 30 minutes and filtered, washing theprecipitates well with water. The crude product is dried overnight invacuo at 90°. Yield: 2.9 g. Percent crude yield: 91.8%.

The crude product is taken up in dioxane (300 ml), treated withactivated carbon while boiling for 10-15 minutes and filtered through acelite pad. The pad is washed with small amounts of dioxane andmethanol, the washings combined with the filtrate and the clear solutionconcentrated down to a volume of 125 ml. The solution is then cooled andthe precipitates that form are filtered off and dried overnight in vacuoat 90°. Yield: 1.86 g., m.p. 284°-285°.

EXAMPLE 2 Pyrazolo[1,5-c]quinazoline-2-carboxylic acid, sodium salt

1.0 g (0.0047 mole) of pyrazolo[1,5-c]-quinazoline-2-carboxylic acid(prepared as described in Example 1) is suspended in 100 ml of water,treated with 394 mg (1 eq) of sodium bicarbonate and stirred overnightat room temperature. The reaction mixture is filtered and the clearfiltrate is treated with activated carbon, heated on a steam bath for 10minutes and filtered through a celite pad, washing the pad well withwater. The washings and filtrate are combined and stripped to dryness.Yield: 0.9 g. Percent crude yield=81.45%.

The crude product is triturated with 12 ml of 50% aqueous methanol andfiltered, washing the white precipitate with a small amount of 50%aqueous methanol. The product is then dried overnight in vacuo at 100°.Yield: 0.72 g, m.p. 400°.

EXAMPLE 3 Pyrazolo[1,5-c]quinazoline-2-carboxylic acid, methyl ester

10.0 g (0.046 mole) of the methyl ester of5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid is suspended in 70 ml of97+% formic acid and heated at 100° for 2 hours. The reaction mixture iscooled, diluted with water (250 ml) and stirred for 10-15 minutes. Theprecipitates are filtered off and washed well with water. The solid isthen taken up in chloroform (500 ml), the residual water layer separatedand the organic layer dried over anhydrous sodium sulfate. The organicphase is filtered and the clear filtrate stripped to dryness. Yield:10.0 g; 96% crude yield (theoretical yield=10.41 g).

The crude product is taken up in 1.25 liter of benzene and the resultingclear solution concentrated down to a volume of 200 ml. Theneedle-shaped crystals are filtered off and dried for 48 hours in vacuoat 55°. Yield: 9.22 g, m.p. 181°-183°.

EXAMPLE 4 5-Methylpyrazolo[1,5-c]quinazoline-2-carboxylic acid, methylester

1.5 g (0.0069 mole) of the methyl ester of5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid is dissolved in amixture of 20 ml of glacial acetic acid and 1.56 ml of acetyl chlorideand stirred overnight at room temperature. The solvent is stripped offand the slurry poured onto 200 ml ice-water and stirred for 30 minutes.The precipitates that form (˜800 mg) are filtered off and air dried.These are then taken up in 30 ml of benzene, filtered while hot and theclear filtrate concentrated down to a volume of 10 ml and cooled. Theproduct is filtered off and dried overnight in vacuo at roomtemperature. Yield: 500 mg, m.p. 155°-156° C.

EXAMPLE 5 5-(Trifluoromethyl)pyrazolo[1,5-c]quinazoline-2-carboxylicacid, methyl ester

500 mg (0.0023 mole) of the methyl ester of5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid is taken up in 10 ml oftrifluoroacetic anhydride and refluxed for 3 hours. (Precipitates startto come out of solution within the first 30 minutes). The reactionmixture is stripped to dryness and the solids obtained are evaporatedtwice from benzene.

The crude product (˜700 mg) is recrystallized from benzene (10 ml) anddried overnight in vacuo at 60°. Yield: 305 mg, m.p. 209°-211°.

EXAMPLE 6 5-Phenylpyrazolo[1,5-c]quinazoline-2-carboxylic acid, methylester

500 mg (0.0023 mole) of the methyl ester of5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid and 5.2 g (0.023 mole)of benzoic anhydride are heated together at 255° for 1 hour and at 150°for 5 hours. The reaction mixture is cooled and the resulting solidtaken up in 40 ml of water and treated portionwise with sodiumbicarbonate. The aqueous solution is layered with 50 ml of methylenechloride and stirred for 30 minutes. The organic layer is thenseparated, dried over anhydrous sodium sulfate and chromatographed on asilica gel column (15 g), eluting the column successively with CH₂ Cl₂(25 ml), CH₂ Cl₂ :EtOAc (8:2, 75 ml) and CH₂ Cl₂ :EtOAc (1:1; 70 ml).

All the fractions containing the product are combined and stripped todryness. The light brown solid is triturated with 20 ml of ether,filtered and dried overnight in vacuo at 60°. Yield: 658 mg, m.p.205°-206°. The crude product is taken up in benzene (50 ml), filteredwhile hot and the clear filtrate concentrated down to a volume of 20 mland cooled. The needle-shaped precipitates are filtered off, washed witha small amount of ether and dried overnight in vacuo at 80°. Yield:423.4 mg, m.p. 201°-203°.

EXAMPLE 7 Pyrazolo[1,5-c]quinazoline-2-methanol, formate ester A.5-(2-Aminophenyl)-1H-pyrazole-3-methanol, hydrochloride

2.0 g (0.0092 mole) of the methyl ester of5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid and 420 mg of 95% LiBH₄are stirred together in 48 ml of distilled tetrahydrofuran at roomtemperature for 36 hours. The reaction mixture is cooled down to 0°,acidified dropwise with 20 ml of 1 N HCl and stirred for 30 minutes. Theacidic suspension is diluted with water (40 ml), stirred for another 15minutes and stripped to dryness. The resulting solid is taken up inabsolute ethanol and filtered through florisil in a sintered glassfunnel, washing the florisil with absolute ethanol (50 ml).

The light yellow filtrate is concentrated down to a syrup which isdissolved in 50 ml of absolute ethanol and treated with 2.9 ml (≅1.1equivalent) of 4 N Et₂ O/HCl and stirred for 30 minutes. The resultingsuspension is diluted further with ether (50 ml), stirred for 10 minutesand filtered. The precipitates are washed well with ether and driedovernight in vacuo at 60°. Yield: 2.2 g, m.p. 217°-218°.

1.2 g of the crude hydrochloride is taken up in hot absolute ethanol (40ml), filtered while hot and the clear filtrate concentrated down to avolume of ˜10 ml. After cooling, the cream-colored precipitates arefiltered off and dried overnight in vacuo at 80°. Yield: 810 mg, m.p.220°-222°.

B. Pyrazolo[1,5-c]quinazoline-2-methanol, formate ester

4.0 g (0.0176 mole) of crude 5-(2-aminophenyl)-1H-pyrazole-3-methanolhydrochloride and 28 ml of 97+% HCOOH are heated at 100° for 5 hours.The reaction mixture is cooled, stripped to dryness and the resultingsolid stirred with water (50 ml) for 30 minutes. The fluffy whiteprecipitates that form are filtered off and air dried. Yield: 3.5 g; 2major spots on TLC. Percent yield (crude): 87.7% (theoretical yield=3.99g).

The crude product is suspended in methylene chloride (30 ml) andchromatographed on a silica gel column (50 g; 1"×11"), eluting thecolumn successively with CH₂ Cl₂ (50 ml), CH₂ Cl₂ :EtOAc (8:2; 100 ml),CH₂ Cl₂ :EtOAc (1:1; 420 ml) and EtOAc (200 ml). The desired fractionsare combined to give 2.87 g of the product. The product from the columnis taken up in benzene (100 ml), the solution filtered while hot, andthe clear filtrate concentrated down to a volume of ˜30 ml and cooled.The fluffy white precipitates are filtered off and dried overnight invacuo at 50°. Yield: 2.35 g, m.p. 118°-120°.

EXAMPLE 8 Pyrazolo[1,5-c]quinazoline-2-methanol

880 mg (0.0039 mole) of the formate ester ofpyrazolo[1,5-c]quinazoline-2-methanol (prepared in Example 7) issuspended in 42.2 ml of 0.1 N NaOH and stirred at room temperature for30 minutes. The precipitates are filtered off, washed with a smallamount of water and air dried. The crude product (1.09) is taken up inethyl acetate (60 ml), filtered while hot and the clear filtrate isconcentrated down to a volume of ˜25 ml and cooled. The needle-shapedprecipitates are filtered off, air dried and combined with a previousbatch, (374.9 mg). The product is then pulverized and the powderobtained dried overnight in vacuo at 60°. Yield: 1.10 g, m.p. 132°-133°.

EXAMPLES 9 TO 17

Following the procedure of Example 1 but substituting the startingmaterial indicated in Column I of Table I set out below for the5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid, the products indicatedin Column II are obtained.

                                      Table I                                     __________________________________________________________________________       Column 1           Column II                                                   ##STR11##                                                                                        ##STR12##                                              Ex.                                                                           No.                                                                              X (position)       X (position)                                            __________________________________________________________________________     9.                                                                              CH.sub.3 (5)      CH.sub.3 (9)                                             10.                                                                              CH.sub.3 (4)      CH.sub.3 (8)                                                Cl(3)             Cl(7)                                                       Br(4)             Br(8)                                                       F(4)              F(8)                                                        CF.sub.3 (5)      CF.sub.3 (9)                                                Cl(6)             Cl(10)                                                      CH.sub.3 O(6)     CH.sub.3 O(10)                                              CH.sub.3 O(5)     CH.sub.3 O(9)                                            __________________________________________________________________________

EXAMPLES 18 TO 26

Following the procedure of Example 2, but substituting the compounds ofExamples 9 to 17 for pyrazolo[1,5-c]quinazoline-2-carboxylic acid, thesodium salts of the compounds of Examples 9 to 17 are obtained.

EXAMPLES 27 TO 36

Following the procedure of Examples 3 to 6, but substituting for themethyl ester of 5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid, thecompound set out in Column I of Table II below and substituting for theacylating agent in Examples 3 to 6, the acylating cyclizing agent shownin Column II, the product shown in Column III is obtained.

                                      TABLE II                                    __________________________________________________________________________    Column I               Column II                                                                              Column III                                     Ex.                                                                              ##STR13##           (1) R.sup.2 COOH(Acylating Agent) (2) (R.sup.2                               CO).sub.2 O                                                                             ##STR14##                                    No.                                                                              X(position)                                                                              R.sup.4  (3) R.sup.2 COHal                                                                      X(position)                                                                         R.sup.4                                                                             R.sup. 2                          __________________________________________________________________________       H          H        (1) CH.sub.3 COOH                                                                      H     .BHorizBrace.                                                                       .BHorizBrace.                                                           as per                                                                              as per                               H          C.sub.2 H.sub.5                                                                        (1) HCOOH                                                                              H     Column I                                                                            Column II                            H          CH.sub.3 (1) C.sub.2 H.sub.5 COOH                                                               H                                                                    (3) C.sub.2 H.sub.5 COCl                               30.                                                                              CH.sub.3 (5)                                                                             C.sub.2 H.sub.5                                                                        (1) CH.sub.3 COOH                                                                      CH.sub.3 (9)                                                         (3) CH.sub.3 COCl                                         CH.sub.3 O(6)                                                                            CH.sub.3 (2) (CF.sub.3 CO).sub.2 O                                                              CH.sub.3 O(10)                                   Cl(4)      C.sub.3 H.sub.7                                                                        (2) (CF.sub.3 CO).sub.2 O                                                              Cl(8)                                            Br(5)      C.sub.2 H.sub.5                                                                        (2) (C.sub.6 H.sub.5 CO).sub.2 O                                                       Br(9)                                            F(3)       CH.sub.3 (2) (C.sub.6 H.sub.5 CO).sub.2 O                                                       F(7)                                             CF.sub.3 (5)                                                                             H        (1) HCOOH                                                                              CF.sub.3 (9)                                     H          CH.sub.3 (2) (C.sub.6 H.sub.5 CO).sub.2                                                         H                                             __________________________________________________________________________

EXAMPLES 37 TO 45

Following the procedure of Example 7, parts A and B, except substitutingfor the methyl ester of 5-(2-aminophenyl)-1H-pyrazole-3-carboxylic acid,the starting material shown in Column I of Table III below, andsubstituting for formic acid, the acylating agent shown in Column II,the product shown in Column III is obtained.

                                      TABLE III                                   __________________________________________________________________________    Column I               Column II                                                                           Column III                                        ##STR15##                                                                                                  ##STR16##                                       Ex.                    R.sup.2 COOH                                           No.                                                                              X(position)                                                                              R.sup.4  R.sup.2                                                                             X(position)                                                                             R.sup.2                                __________________________________________________________________________       CH.sub.3 (5)                                                                             C.sub.2 H.sub.5                                                                        H     CH.sub.3 (9)                                                                            .BHorizBrace.                                                                 as per                                    CH.sub.3 (4)                                                                             CH.sub.3 C.sub.2 H.sub.5                                                                     CH.sub.3 (8)                                                                            Column II                                 Cl(3)      CH.sub.3 CF.sub.3                                                                            Cl(7)                                            40.                                                                              Br(4)      C.sub.3 H.sub.7                                                                        C.sub.6 H.sub.5                                                                     Br(8)                                               F(4)       C.sub.2 H.sub.5                                                                        CH.sub.3                                                                            F(8)                                                CF.sub.3 (5)                                                                             CH.sub.3 CF.sub.3                                                                            CF.sub.3 (9)                                        Cl(6)      C.sub.3 H.sub.7                                                                        H     Cl(10)                                              CH.sub.3 O(6)                                                                            CH.sub.3 H     CH.sub.3 O(10)                                      CH.sub.3 O(5)                                                                            C.sub.4 H.sub.9                                                                        C.sub.2 H.sub.5                                                                     CH.sub.3 O(9)                                    __________________________________________________________________________

EXAMPLES 46 TO 54

Following the procedure of Example 8, except substituting for theformate ester of pyrazolo[1,5-c]quinazoline-2-methanol, the ester shownin Examples 37 to 45, the correspondingpyrazolo[1,5-c]quinazoline-2-methanol is obtained.

What is claimed is:
 1. A compound of the structure ##STR17## wherein R¹is carboxyl; hydroxymethyl; CO₂ R³ wherein R³ is lower alkyl, Li⁺, Na⁺or K⁺ ; or ##STR18## R² is hydrogen, lower alkyl, phenyl, lower alkylphenyl, di (lower alkyl) phenyl, halophenyl, or trifluoromethyl; and Xis hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl. 2.The compound of claim 1 wherein R¹ is carboxyl.
 3. The compound of claim1 wherein R¹ is hydroxymethyl.
 4. The compound of claim 1 wherein R¹ isCO₂ R³.
 5. The compound of claim 4 wherein R³ is Li⁺, Na⁺, or K⁺.
 6. Thecompound of claim 4 wherein R³ is methyl.
 7. The compound of claim 1wherein R¹ is ##STR19##
 8. The compound of claim 7 wherein R² is H. 9.The compound of claim 1 having the namepyrazolo[1,5-c]quinazoline-2-carboxylic acid.
 10. The compound of claim1 having the name pyrazolo[1,5-c]quinazoline-2-carboxylic acid, sodiumsalt.
 11. The compound of claim 1 having the namepyrazolo[1,5-c]quinazoline-2-carboxylic acid, methyl ester.
 12. Thecompound of claim 1 having the name5-methylpyrazolo[1,5-c]quinazoline-2-carboxylic acid, methyl ester. 13.The compound of claim 1 having the name5-phenylpyrazolo[1,5-c]quinazoline-2-carboxylic acid, methyl ester. 14.The compound of claim 1 having the name5-(trifluoromethyl)pyrazolo[1,5-c]quinazoline-2-carboxylic acid, methylester.
 15. The compound of claim 1 having the namepyrazolo[1,5-c]quinazoline-2-methanol, formate ester.
 16. The compoundof claim 1 having the name pyrazolo[1,5-c]quinazoline-2-methanol.
 17. Apharmaceutical composition for use in treating allergic conditionscomprising a compound as defined in claim 1 and a pharmaceuticallyacceptable carrier therefor.
 18. A method for treating allergicconditions in mammals, which comprises administering to the mammalianhost a therapeutic amount of a compound as defined in claim 1.